Department of Medicinal and Applied Chemistry, College of Life Sciences, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan.
ACS Appl Bio Mater. 2021 Apr 19;4(4):3264-3275. doi: 10.1021/acsabm.0c01621. Epub 2021 Mar 26.
Combining upconversion nanoparticles (UCNPs) and UV-sensitive polymers to form a smart drug delivery system (DDS) is a promising strategy to circumvent drawbacks of direct UV excitation in clinical applications. This study tuned up core-shell UCNPs with a shell thickness of 6 nm and emission wavelength falling in the ultraviolet region at 350 nm under near-infrared (NIR) light irradiation at 980 nm. An amphiphilic block copolymer with UV-responsive -nitrobenzyl ester (ONB) next to a glutathione (GSH)-responsive disulfide linkage was synthesized and formulated into a polymersome. Core-shell UCNPs and doxorubicin (DOX) were simultaneously encapsulated into the polymersome during double emulsion for DDS. The combination of NIR light-inducing photolysis of the ONB linkage and GSH cleaving the disulfide linkage enhanced DOX release for chemotherapy. From evaluation, the polymersome alone was nontoxic against three lung cancer cell lines, but the one loaded with core-shell UCNPs and DOX showed severe cell-killing effect under the assistance of a 980 nm diode laser. study in A549 tumor-bearing mice verified significant inhibition of tumor growth in mice treated with the polymersome containing core-shell UCNPs and DOX under 980 nm diode laser irradiation as compared with those without laser irradiation and those treated with free DOX. This intriguing nanomedicine of well-defined structures responsive to NIR light and reducing agents offers potential for smart DDS applications.
将上转换纳米粒子（UCNPs）与对紫外光敏感的聚合物结合起来，形成智能药物传递系统（DDS），是克服临床应用中直接紫外光激发的缺点的一种很有前途的策略。本研究通过在近红外（NIR）光照射下（980nm），将壳层厚度为 6nm、发射波长在紫外光区（350nm）的核壳型 UCNPs 进行调谐。合成了一种具有紫外光响应的-硝基苄酯（ONB）和谷胱甘肽（GSH）响应的二硫键的两亲性嵌段共聚物，并将其制成聚合物囊泡。在双重乳液中，同时将核壳型 UCNPs 和阿霉素（DOX）包封到聚合物囊中，用于 DDS。ONB 键的 NIR 光诱导光解和 GSH 切断二硫键的协同作用增强了化疗的 DOX 释放。评估结果表明，聚合物囊泡本身对三种肺癌细胞系没有毒性，但在 980nm 二极管激光的辅助下，负载核壳型 UCNPs 和 DOX 的聚合物囊泡显示出严重的细胞杀伤作用。在 A549 荷瘤小鼠中的研究表明，与未进行激光照射和未进行激光照射且用游离 DOX 治疗的小鼠相比，用含有核壳型 UCNPs 和 DOX 的聚合物囊泡治疗的小鼠，肿瘤生长受到显著抑制。这种结构明确的、对近红外光和还原剂有响应的新型纳米医学为智能 DDS 应用提供了潜力。
